BACKGROUND: The efficacy and tolerability of two different schedules of paclitaxel, carboplatin, and trastuzumab (PCarH) for HER2-positive, locally aggressive (stage IIB-IIIC) breast cancers were evaluated in this phase II trial. METHODS: Patients were randomly assigned to receive either weekly (12 doses over 16 weeks) or once-every-3-weeks (4 doses over 12 weeks) treatment. The primary endpoint was pathologic complete remission (pCR) in the breast and axilla. To detect an assumed 35% pCR absolute difference between the two schedules, a minimum of 26 assessable patients in each group was required (two-sided α = 0.05, β = 0.2). RESULTS: A total of 56 patients were enrolled (weekly group, n = 29; every-3-weeks group, n = 27). In the intent-to-treat analysis, pCR in the breast/axilla were found in 31 patients (55%; 95% confidence interval [CI]: 41%-69%). Compared with the every-3-weeks schedule, the weekly administration achieved higher pCR (41% vs. 69%; p = .03). After adjustment for clinical and pathological factors, the weekly administration was more effective than the every-3-weeks schedule, with hazard ratio of 0.3 (95% CI: 0.1-0.9; p = .03). Interestingly, weekly administration resulted in high pCR rates in both luminal-B (HER2-positive) and ERBB2+ tumors (67% vs. 71%; p = .78), whereas luminal-B (HER2-positive) tumors benefited less from the every-3-weeks schedule compared with the ERBB2+ tumors (21% vs. 62%, p = .03). These results remain after multivariate adjustment, showing weekly administration was more effective in the luminal-B (HER2-positive) subgroup (p = .02) but not in the ERBB2+ subgroup (p = .50). CONCLUSION: A more frequent administration might improve the possibility of eradicating invasive cancer in the breast and axilla, especially in the luminal-B (HER2-positive) subtype. Further studies to validate our findings are warranted.
RCT Entities:
BACKGROUND: The efficacy and tolerability of two different schedules of paclitaxel, carboplatin, and trastuzumab (PCarH) for HER2-positive, locally aggressive (stage IIB-IIIC) breast cancers were evaluated in this phase II trial. METHODS:Patients were randomly assigned to receive either weekly (12 doses over 16 weeks) or once-every-3-weeks (4 doses over 12 weeks) treatment. The primary endpoint was pathologic complete remission (pCR) in the breast and axilla. To detect an assumed 35% pCR absolute difference between the two schedules, a minimum of 26 assessable patients in each group was required (two-sided α = 0.05, β = 0.2). RESULTS: A total of 56 patients were enrolled (weekly group, n = 29; every-3-weeks group, n = 27). In the intent-to-treat analysis, pCR in the breast/axilla were found in 31 patients (55%; 95% confidence interval [CI]: 41%-69%). Compared with the every-3-weeks schedule, the weekly administration achieved higher pCR (41% vs. 69%; p = .03). After adjustment for clinical and pathological factors, the weekly administration was more effective than the every-3-weeks schedule, with hazard ratio of 0.3 (95% CI: 0.1-0.9; p = .03). Interestingly, weekly administration resulted in high pCR rates in both luminal-B (HER2-positive) and ERBB2+ tumors (67% vs. 71%; p = .78), whereas luminal-B (HER2-positive) tumors benefited less from the every-3-weeks schedule compared with the ERBB2+ tumors (21% vs. 62%, p = .03). These results remain after multivariate adjustment, showing weekly administration was more effective in the luminal-B (HER2-positive) subgroup (p = .02) but not in the ERBB2+ subgroup (p = .50). CONCLUSION: A more frequent administration might improve the possibility of eradicating invasive cancer in the breast and axilla, especially in the luminal-B (HER2-positive) subtype. Further studies to validate our findings are warranted.
Authors: H M Kuerer; L A Newman; T L Smith; F C Ames; K K Hunt; K Dhingra; R L Theriault; G Singh; S M Binkley; N Sneige; T A Buchholz; M I Ross; M D McNeese; A U Buzdar; G N Hortobagyi; S E Singletary Journal: J Clin Oncol Date: 1999-02 Impact factor: 44.544
Authors: Edwin R Fisher; Jiping Wang; John Bryant; Bernard Fisher; Eletherios Mamounas; Norman Wolmark Journal: Cancer Date: 2002-08-15 Impact factor: 6.860
Authors: Marco Colleoni; Giuseppe Viale; David Zahrieh; Giancarlo Pruneri; Oreste Gentilini; Paolo Veronesi; Richard D Gelber; Giuseppe Curigliano; Rosalba Torrisi; Alberto Luini; Mattia Intra; Viviana Galimberti; Giuseppe Renne; Franco Nolè; Giulia Peruzzotti; Aron Goldhirsch Journal: Clin Cancer Res Date: 2004-10-01 Impact factor: 12.531
Authors: Joseph A Sparano; Molin Wang; Silvana Martino; Vicky Jones; Edith A Perez; Tom Saphner; Antonio C Wolff; George W Sledge; William C Wood; Nancy E Davidson Journal: N Engl J Med Date: 2008-04-17 Impact factor: 91.245
Authors: A H Calvert; S J Harland; D R Newell; Z H Siddik; A C Jones; T J McElwain; S Raju; E Wiltshaw; I E Smith; J M Baker; M J Peckham; K R Harrap Journal: Cancer Chemother Pharmacol Date: 1982 Impact factor: 3.333
Authors: Mark D Pegram; Tadeusz Pienkowski; Donald W Northfelt; Wolfgang Eiermann; Ravi Patel; Pierre Fumoleau; Eleonor Quan; John Crown; Deborah Toppmeyer; Michael Smylie; Alessandro Riva; Sandra Blitz; Michael F Press; David Reese; Mary-Ann Lindsay; Dennis J Slamon Journal: J Natl Cancer Inst Date: 2004-05-19 Impact factor: 13.506
Authors: Priya Rastogi; Stewart J Anderson; Harry D Bear; Charles E Geyer; Morton S Kahlenberg; André Robidoux; Richard G Margolese; James L Hoehn; Victor G Vogel; Shaker R Dakhil; Deimante Tamkus; Karen M King; Eduardo R Pajon; Mary Johanna Wright; Jean Robert; Soonmyung Paik; Eleftherios P Mamounas; Norman Wolmark Journal: J Clin Oncol Date: 2008-02-10 Impact factor: 44.544
Authors: Harold J Burstein; Lyndsay N Harris; Rebecca Gelman; Susan C Lester; Raquel A Nunes; Carolyn M Kaelin; Leroy M Parker; Leif W Ellisen; Irene Kuter; Michele A Gadd; Roger L Christian; Patricia Rae Kennedy; Virginia F Borges; Craig A Bunnell; Jerry Younger; Barbara L Smith; Eric P Winer Journal: J Clin Oncol Date: 2003-01-01 Impact factor: 44.544